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Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and fixed airflow obstruction. Patients with COPD have increased risk of lung cancer (LC), and the coexistence of both diseases is associated with poorer survival. However, the mechanisms predisposing patients with COPD to LC development and poor prognosis remain unclear. Gene expression profiles were downloaded from the Gene Expression Omnibus. Twenty‐two data sets were included (n = 876). We identified 133 DEGs and 145 DEGs in patients with COPD and LC compared with healthy controls, respectively. There were 1544 DEGs in patients with LC and coexisting COPD compared with COPD, and these DEGs are mainly involved in the cell cycle, DNA replication, p53 signalling and insulin signalling. The biological processes primarily associated with these DEGs are oxidation reduction and apoptosis. SPP1 was the only overlapping DEG that was up‐regulated in patients with COPD and/or LC, and this was validated by qPCR in an independent cohort. The area under the curve value for SPP1 was 0.893 (0.822–0.963) for the prediction of LC in patients with COPD. High expression of SPP1 in patients with LC was associated with shorter survival time. Up‐regulation of SPP1 may be associated with increased risk of LC in patients with COPD and therefore may have potential as a therapeutic target for LC in patients with COPD., SPP1 is progressively up‐regulated in the lungs of patients with COPD, lung cancer (LC) and LC coexisting with COPD, as shown by bioinformatic analysis. Up‐regulation of SPP1 expression in COPD and its further up‐regulation in NSCLC coexisting with COPD were confirmed by qPCR. The area under the curve value for SPP1 was 0.893 (0.822–0.963) for the prediction of LC in patients with COPD. Thus, up‐regulation of SPP1 may be associated with increased risk of LC in patients with COPD.

Background The 6 gene expression signature (6GS) predicts inflammatory phenotype, exacerbation risk, and corticosteroid responsiveness in asthma. In COPD, patterns of airway inflammation are similar, suggesting the 6GS may be useful. This study determines the diagnostic and prognostic ability of 6GS in predicting inflammatory phenotypes and exacerbation risk in COPD. Methods We performed 2 studies: a cross-sectional phenotype prediction study in stable COPD (total N=132; n=34 eosinophilic (E)-COPD, n=42 neutrophilic (N)-COPD, n=39 paucigranulocytic (PG)-COPD, n=17 mixed-granulocytic (MG)-COPD) that assessed 6GS ability to discriminate phenotypes (eosinophilia≥3%; neutrophilia≥61%); and a prospective cohort study (total n=54, n=8 E-COPD; n=18 N-COPD; n=20 PG-COPD; n=8 MG-COPD, n=21 exacerbation prone (≥2/year)) that investigated phenotype and exacerbation prediction utility. 6GS was measured by qPCR and evaluated using multiple logistic regression and area under the curve (AUC). Short-term reproducibility (intra-class correlation) and phenotyping method agreement (κ statistic) were assessed. Results In the phenotype prediction study, 6GS could accurately identify and discriminate patients with E-COPD from N-COPD (AUC=96.4%; p

Dyspnea is one of the most common symptoms of chronic respiratory disease (CRD) and is closely related to increased functional disability and mortality, resulting in substantial adverse outcomes on patients and imposing great social and economic burden. Although multiple clinical trials and systematic reviews have suggested that acupuncture could be effective in treating COPD and lung cancer, little is known about its effects on dyspnea relief in patients with CRD. The present study aimed to use a systematic review approach to evaluate the effectiveness and safety of acupuncture in the treatment of dyspnea in patients with CRD.We will search the following 9 databases from inception to June 30, 2022, PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, WANFANG Database, Chinses Scientific and Technological Periodical Database, and Chinese Biomedical Database, and the Cochrane Library Database. Clinical randomized controlled trials in English or Chinese that evaluate invasive acupuncture versus control group in treatment of CRD with dyspnea will be included. The primary outcome will be dyspnea scores, breathing physiological function, and the secondary outcomes include exercise tolerance by six-minute walk distance quality of life, quality of life and adverse events. Two reviewers will independently conduct study selection, data extraction and quality assessment. The Review Manager software will be used for meta-analysis. This protocol will be carried out in accordance with the PRISMA-P guidance.This systematic review and meta-analysis will provide the evidence of whether acupuncture is an effective and safe intervention for CRD with dyspnea. The results will be disseminated through peer-reviewed publication.

Osteoarthritis (OA) is not only related to the degradation of articular cartilage, but also possibly to the changes of subchondral bone. The purpose of this study was to assess whether specific differences could be resolved from bone composition, as also contributed to OA. These differences were assessed by using Fourier transform infrared spectroscopy (FTIRS). The main parameters including mineral content, carbonate content, crystallinity, collagen cross-linking ratio (XLR) and acid phosphate content were represented with characteristic peak integration. It was found that mineral and carbonate content varied significantly with depths at different OA stages. Mineral content increased with depth in healthy samples, while carbonate content showed opposite trend. The mineral content reduced obviously with OA duration, which was different with carbonate decreasing only at early stage of OA. In addition, the content of acid phosphate, collagen maturity (XLR) and crystallinity slight varied with the OA aggravation. Therefore, the changes in subchondral bone were significantly associated with cartilage degeneration and OA, the associated parameters should be targeted for OA therapies.

IntroductionIncreasing numbers of patients with non-haematological diseases are infected with invasive pulmonary aspergillosis (IPA), with a high mortality reported which is mainly due to delayed diagnosis. The diagnostic capability of mycological tests for IPA including galactomannan test, (1,3)-β-D-glucan test, lateral flow assay, lateral flow device and PCR for the non-haematological patients remains unknown. This protocol aims to conduct a systematic review and meta-analysis of the diagnostic performance of mycological tests to facilitate the early diagnosis and treatments of IPA in non-haematological diseases.Methods and analysisDatabase including PubMed, CENTRAL and EMBASE will be searched from 2002 until the publication of results. Cohort or cross-sectional studies that assessing the diagnostic capability of mycological tests for IPA in patients with non-haematological diseases will be included. The true-positive, false-positive, true-negative and false-negative of each test will be extracted and pooled in bivariate random-effects model, by which the sensitivity and specificity will be calculated with 95% CI. The second outcomes will include positive (negative) likelihood ratio, area under the receiver operating characteristic curve and diagnostic OR will also be computed in the bivariate model. When applicable, subgroup analysis will be performed with several prespecified covariates to explore potential sources of heterogeneity. Factors that may impact the diagnostic effects of mycological tests will be examined by sensitivity analysis. The risk of bias will be appraised by the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2).Ethics and disseminationThis protocol is not involved with ethics approval, and the results will be peer-reviewed and disseminated on a recognised journal.PROSPERO registration numberCRD42021241820.

Background: Chronic obstructive pulmonary disease (COPD) and lung cancer often coexist, which is associated with a worse prognosis. Thousands of biomarkers related to the survival of lung cancer have been investigated. However, those which can predict the survival of lung cancer coexisting with COPD are currently lacking. The present study aimed to identify novel gene signatures to predict the survival of patients with lung cancer coexisting COPD.Method: RNA-sequence data of lung cancer and control accompanying with matched clinical information were retrieved from the Cancer Genome Atlas (TCGA). Differently expressed genes (DEGs) associated with lung cancer coexisting COPD were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Univariate and multivariate Cox regression analyses were applied to identify survival-associated DEGs and to construct survival-associated gene signature. Kaplan-Meier survival analysis and calibration plots of the nomogram were performed to test the predictive accuracy of the gene signature. qPCR was performed to validate the genes in the prognostic signature.Results: Sequence data from 70 patients with lung cancer coexisting COPD, 127 with lung cancer alone and 108 control tissues were included for analysis. A total of 2424 DEGs were identified when comparing lung cancer coexisting COPD with controls. The biological process was primarily associated with DNA-binding transcription activator activity, peptidase inhibitor activity, endopeptidase inhibitor activity, et al. KEGG pathways were mainly enriched in neuroactive ligand-receptor interaction, cell cycle, and Staphylococcus aureus infection. A survival-associated gene signature consisting of CEACAM5, RASAL1, CSTL1, CNGB1, and SLC4A3 was identified and represented as risk score. The high-risk score group had significantly worse survival than the low-risk score group (P < 0.001). Areas under receiver operating characteristic curves were 0.943, 0.773, 0.888 for predicting overall survival at 1-, 3-, and 5-year, respectively. The risk score was an independent predictor of survival, independent of clinical factors. High conformity of the actual survival and the nomogram–predicted probability of survival by applying the risk score. Upregulation of the five genes in patients with lung cancer coexisting COPD were confirmed by qPCR in an independent cohort.Conclusion: Our study constructed and validated a novel prognostic gene signature for predicting survival of patient with lung cancer coexisting COPD, which may contribute to the clinical treatment decisions.

A home-made small-sized Raman spectrometer combined with machine learning algorithms was used to study and identify healthy and multi-period osteoarthritis (OA) canine knee joints. Nine canines were equally divided into three groups according to the post-operative (OA modeling) time of 2-month, 3-month and 7-month. Other two normal canines were used as control. It was found that the degeneration degree of cartilage was positively correlated with post-operative time by doing anatomical analysis. The mixed Raman spectra of cartilage and subchondral bone were collected and analyzed, which reveals subchondral bone demineralization and carbonate ion substituting into the apatite mineral during OA. Raman spectra combined with principal component analysis (PCA) further disclosed that collagen matrix became unordered, both content ratios of amide I/matrix and phenylalanine/matrix in OA cartilage and subchondral bone increased. Based on the PCA getting five principal components, all groups were effectively discriminated by Fisher discriminant analysis (FDA) with high accuracy of 91.07% for the validation set, as well as 95.45% for the test set. It suggests that Raman spectroscopy combined with machine learning is capable to become an effective tool to achieve in situ identification of multi-period OA with high accuracy and preclinical significance.

Deep learning is usually combined with a single detection technique in the field of disease diagnosis. This study focused on simultaneously combining deep learning with multiple detection technologies, fluorescence imaging and Raman spectroscopy, for breast cancer diagnosis. A number of fluorescence images and Raman spectra were collected from breast tissue sections of 14 patients. Pseudo-color enhancement algorithm and a convolutional neural network were applied to the fluorescence image processing, so that the discriminant accuracy of test sets, 88.61%, was obtained. Two different BP-neural networks were applied to the Raman spectra that mainly comprised collagen and lipid, so that the discriminant accuracy of 95.33% and 98.67% of test sets were gotten, respectively. Then the discriminant results of fluorescence images and Raman spectra were counted and arranged into a characteristic variable matrix to predict the breast tissue samples with partial least squares (PLS) algorithm. As a result, the predictions of all samples are correct, with minor error of predictive value. This study proves that deep learning algorithms can be applied into multiple diagnostic optics/spectroscopy techniques simultaneously to improve the accuracy in disease diagnosis.

Background. Chinese oral herbal paste has been widely used in the treatment of chronic obstructive pulmonary disease (COPD). However, the treatment effects of herbal paste were controversial and lack evidence to support its clinical use. This study aims to systematically assess the efficacy and safety of Chinese oral herbal paste for the treatment of stable COPD. Methods. PubMed, Web of Science, CENTRAL, EMBASE, CNKI, VIP, CBM, and WANFANG database in addition to two websites of clinical trial registry were searched from respective inception to August 2019. Only randomized controlled trials (RCTs) studying Chinese herbal paste for the treatment of stable COPD were included. Methodological quality was assessed based on Cochrane risk of bias and GRADE approach. Data were analyzed using RevMan 5.3. Results. A total of 19 RCTs with 1303 individuals compared Chinese oral herbal paste and Western medicine (WM) with WM alone were included for meta-analysis. The review showed compared with WM alone, the combination of herbal paste and WM reduced exacerbation frequency. Subgroup analyses showed that after two to three months of treatment, compared with WM alone, Chinese herbal paste plus WM significantly decreased the St George’s Respiratory Questionnaire (SGRQ) scores, COPD assessment test (CAT) scores, and scores of traditional Chinese medicine (TCM) syndrome, and improved clinical effective rates, lung function, and 6-minute walk distance. No serious adverse events related to herbal paste were reported. Conclusion. Current evidence showed that Chinese oral herbal paste may be an effective and well-tolerated adjuvant therapy for stable COPD. Considering the risks of bias and heterogeneity, more high-quality, well-designed RCTs are still needed.

As the most common cancer in women, breast cancer is becoming lethal worldwide. However, the current breast diagnosis technologies are not enough to meet the requirements in clinic due to some shortages of early-stage insensitiveness, time consumption and relying on the doctor's experience, etc. It's necessary to develop a creative method for the automatical diagnosis of breast cancer. Therefore, Raman spectroscopy and one-dimensional convolutional neural network (1D-CNN) algorithm were combined together for the first time to classify the healthy and cancerous breast tissues in this study. First, a number of Raman spectra were collected from breast samples of 20 patients for spectral analysis. Then, a 1D-CNN model was developed and trained for classification. In addition, the Fisher Discrimination Analysis (FDA) and Support Vector Machine (SVM) classifiers were trained and tested with the same spectral data for comparison. The best classification performance, namely the overall diagnostic accuracy of 92%, the sensitivity of 98% and the specificity of 86%, has been achieved by using 1D-CNN model. This study proves that 1D-CNN combined with Raman spectroscopy can classify breast tissues effectively and automatically and lay the foundation for automated cancer diagnosis in the future.

Objective Randomized clinical trials and published meta-analyses assessing the clinical effectiveness of Chinese herbal medicine (CHM) on the treatment of stable chronic obstructive pulmonary disease (COPD) yielded inconsistent results in terms of disease outcomes, in which the design of placebo-controlled studies can contribute to the heterogeneity. This study aimed to evaluate the efficacy and safety of CHM compared to placebo on the treatment of stable COPD, to provide robust evidence for the use of CHM in COPD. Methods Nine electronic databases were searched from inception to October 1, 2019 to identify placebo controlled randomized trials of CHM for the treatment of stable COPD and studies in English or Chinese were included. The primary outcomes were symptom score (CAT score), quality of life (SGRQ) and frequency of acute exacerbations. The secondary outcomes included lung function, clinical total effective rate and adverse events. The selection of studies, data extraction and coding and assessment of risk of bias of the included studies were conducted by two reviewers independently. Mean difference (MD) was used to analyze continuous variable and relative risk ratio (RR) for dichotomous data. Results A total of eleven studies involving 1223 patients were included. While maintaining routine western pharmacotherapies (WP), CHM had significant advantage over the treatment of placebo in improving CAT score (MD -3.93; 95 %CI -6.01 to -1.85) and SGRQ score (MD -6.20; 95 %CI -10.13 to -2.28), reducing the frequency of acute exacerbations (MD -0.78; 95 %CI -1.40 to -0.16) and improving clinical effective rate (RR 1.29; 95 %CI 1.14 to 1.45), but had no significant effect on improving FEV1%pred (MD 8.18; 95 %CI -4.22 to 20.58). High heterogeneity was found for the changes in exacerbation frequency and FEV1%pred. No serious adverse events related to CHM were reported. Conclusions This meta-analysis of placebo-controlled RCTs demonstrated that the use of CHM in addition to WP could alleviate clinical symptoms, improve quality of life and clinical efficiency and reduce the frequency of exacerbations, which could be an alternative approach for treatment adjustment of COPD. CHM was a relatively safe treatment. These findings need to be verified in future with high-quality clinical trials.

Background and objective T lymphocytes, which are characterized by longevity and immune memory, play an important role in airway inflammation in asthma. Here, we assessed the association between immune memory and histone deacetylation and/or acetylation status. Methods CD4 + CD45RBlow cells (memory T (Tm)) obtained from the spleens of asthma mice models were co-cultured with glucocorticoids (GCs), trichostatin A (TSA) or anacardic acid (AA) and adoptively transferred to naive mice. Interleukin (IL)-4, 5 and 13 and IFN-γ concentrations were measured in culture supernatants and bronchoalveolar lavage fluid (BALF). Histone deacetylase (HDAC) and histone acetyltransferase (HAT) activities and the expression of T-bet, GATA-3, HDACs 1–11 and alveolar eosinophilic inflammation index (AEII) were determined in lung tissues. Results Culture supernatants and the BALF showed similar cytokine profiles. AA and GCs significantly inhibited HAT activity (P = 0.002 and P = 0.018), whereas TSA inhibited and GCs promoted HDAC activity (P = 0.004 and P = 0.025). HDACs 7, 9 and 10 were upregulated by AA and GCs (all P

Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear.Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed. Sputum mast cell subtypes were determined by molecular phenotyping based on expression of mast cell biomarkers (tryptase (TPSAB1), chymase (CMA1) and carboxypeptidase A3 (CPA3)). Effects of mast cell subtypes on steroid response were observed in a prospective cohort study (n=50).MCT (n=18) and MCT/CPA3 (mRNA expression of TPSAB1 and CPA3; n=29) subtypes were identified, as well as a group without mast cell gene expression (n=8). The MCT/CPA3 subtype had elevated exhaled nitric oxide fraction, sputum eosinophils, bronchial sensitivity and reactivity, and poorer asthma control. This was accompanied by upregulation of 13 genes. Multivariable logistic regression identified CPA3 (OR 1.21, p=0.004) rather than TPSAB1 (OR 0.92, p=0.502) as a determinant of eosinophilic asthma. The MCT/CPA3 subtype had a better clinical response and reduced signature gene expression with corticosteroid treatment.Sputum mast cell subtypes of asthma can be defined by a molecular phenotyping approach. The MCT/CPA3 subtype demonstrated increased bronchial sensitivity and reactivity, and signature gene expression, which was associated with airway eosinophilia and greater corticosteroid responsiveness.

Submillimetric hollow fiber (HOF-) attenuated total reflection (ATR-) Fourier transform infrared spectroscopy (FTIRS) technique is very suitable for in situ detection of biological samples. HOF-ATR-FTIRS analysis discloses that the significant changes in collagen fiber and proteoglycan between healthy and osteoarthritic (OA) canine specimens. The technique combined with principal component analysis (PCA) and Fisher’s discriminant analysis (FDA) was used to further identify in situ healthy and OA cartilage specimens. The sensitivity of 100% and specificity of 93.6% were obtained for prediction group after all the cases were correctly identified for initial sample, and cross validation was identified with 100% accuracy. The HOF-ATR-FTIRS technique is convenient for operation and suitable for micro-area in situ diagnosis, while the FDA method is fast and accurate. The combination of HOF-ATR-FTIR technique and FDA method can fast realize the micro-area detection and classification of in situ samples with good accuracy, which has potential ability to provide a practical clinical diagnosis of OA.

Background: The activation of NLRP3 inflammasome is involved in the aggravated inflammatory response of COPD exacerbations. However, there is a lack of treatment options targeting this specific pathway while andrographolide is shown to benefit certain inflammatory diseases by reducing IL-1β production. Objective: This study aims to examine the effect of andrographolide on the NLRP3 inflammasome pathway activation in COPD. Methods: THP-1 monocytes were stimulated with PMA to induce monocyte-to-macrophage differentiation. THP-1 macrophages were treated with andrographolide on concentrations of 10, 20 and 40 µmol/L for 1h, followed by stimulation of LPS for 24h and ATP for 1h to activate NLRP3 inflammasome. Positive and negative control were established by interfering cells with NLRP3 specific siRNA and DMSO respectively. PBMCs were isolated from COPD patients’ peripheral blood and incubated with GM-CSF for macrophage differentiation. Macrophages were treated with andrographolide and stimulated with LPS+ATP as previously described. Cell culture supernatants were collected for IL-1β assay, and cells were harvested for NRLP3, ASC, Caspase-1 and IL-1β gene and protein assays by qPCR and Western-blot. Results: Andrographolide significantly downregulated NLRP3, Caspase-1 and IL-1β gene expression and protein levels in THP-1 macrophages. In COPD, 20 and 40 µmol/L of andrographolide significantly inhibited NLRP3 inflammasome activation manifested by the decreased protein levels of NLRP3, Caspase-1 and IL-1β production in monocytes-derived macrophages. Conclusion: Natural product andrographolide inhibited the NLRP3 inflammasome activation in COPD and might be a potential strategy to target COPD excerbations.

Background: The elevation of IL-1β levels in COPD patients is involved in the inflammatory response of the disease. However, the upstream mechanism remains unclear and NLRP3 inflammasome activation might be implicated. Objective: To examine the hypothesis that the NLRP3 inflammasome pathway is upregulated which leads to an over-production of IL-1β in COPD. Methods: A total of 61 participants were recruited including patients with stable COPD (n=29) and healthy controls (HC, n=32). Patients with stable COPD were re-recruited at acute exacerbations. Spirometry, sputum induction were performed and blood was collected at each visit. The expression levels of genes including NLRP3, ASC, CASP1 and IL1B and the level of IL-1β protein were assayed in both sputum and blood and were compared between stable COPD vs HC, and between stable vs exacerbated COPD. Results: The levels of NLRP3(P=0.032), CASP1(P=0.019) and IL1B(P=0.039) gene expression in sputum were significantly elevated in patients with stable COPD compared to HC, and the levels tended to be further elevated when patients experienced exacerbations. The levels of IL-1β in sputum were elevated in patients with stable COPD (319.97(202.54-425.28)ng/mL) versus HC (94.98(53.92-133.34)ng/mL)(P Conclusion: COPD patients had upregulated level of NLRP3 inflammasome induced IL-1β pathway. This pathway activation represents the innate immune and inflammatory response in the local airway but not a systemic inflammation.

Invasive pulmonary aspergillosis (IPA) has been increasingly reported in patients with underlying respiratory diseases (URD). Early diagnosis of IPA is crucial for mortality reduction and improved prognosis, yet remains difficult. Existing diagnostic tools for IPA largely rely on the detection of biomarkers based on serum or bronchoalveolar lavage fluid (BALF), both of which have their limitations. The use of sputum sample is non-invasive, and Aspergillus detection is feasible; however, the usefulness of sputum biomarkers for the diagnosis of IPA, especially in patients with URD, has not been systematically studied. This is a prospective diagnostic trial. At least 118 participants will be recruited from respiratory wards and intensive care units. IPA is defined according to the EORTC/MSG criteria modified for patients with URD. Induced sputum and blood will be collected, and BALF will be obtained by bronchoscopy. Sputum biomarkers, including galactomannan, Aspergillus DNA, triacetylfusarinine and bis(methylthio)gliotoxin will be determined, and the presence of a JF5 antigen will be examined with a lateral fluid device. The sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratio will be computed for different biomarkers and compared using the McNemar χ2 test. Receiver operating characteristic analyses will be performed, and the cut-off values will be established. Participants will receive follow-up evaluations at 3 months and 6 months after recruitment. The difference in hospital stay and survival will be analysed, and the relationships between the levels of biomarkers and hospital stay and survival will be analysed via regression models. We have developed and verified the feasibility of Aspergillus-related biomarker assays for sputum. The study findings will contribute to a novel look at the diagnostic performance of sputum biomarkers in IPA and provide important insight into the improvement of the early diagnosis of IPA, particularly in patients with URD. This study has been registered with the Chinese Clinical Trial Registry ( ChiCTR-DPD-16009070 ) on 24th of August 2016.

Background: The 2017 GOLD report refined combined assessment and proposed pharmacologic strategy. Aims: To apply the new GOLD classification to a Chinese cohort, and to assess the concordance of current medication use according to the new assessment and levels of circulating inflammatory markers. Methods: Patients (n=222) with COPD underwent a combined assessment of symptoms (mMRC or CAT) and exacerbation history in a cross-sectional study. Medication use and medical history were recorded. Serum levels of CRP, IL-6, IL-8 and TNF-α were determined using ELISA. Patients were classified as group A, B, C and D based on the combined assessment. Clinical characteristics, medication use and levels of inflammatory markers were compared among groups. Results: In groups A, B, C and D, there were 5(2.3%), 29(13.1%), 13(5.9%) and 62(78.8%) patients respectively. Age, sex, BMI and smoking history did not differ among the groups. Patients in group B and D had higher scores of hospital depression scale than that in group C (P=0.008). Charlson comorbidity index was greater in group D than group C (P=0.007). The distribution of group A to D changed to 16(7.2%), 18(8.1%), 53(23.9%) and 135(60.8%) when symptoms were assessed using mMRC only. LAMA or ICS/LABA or triple therapy was used in 55.1%, 15.4% and 58.3% of groups B, C and D respectively. Levels of Inflammatory markers were not different among groups. Conclusion: Patients in ‘more symptoms’ groups were associated with deteriorated depression status and high comorbidity. Symptom assessment using mMRC only led to a reduction in symptom severity. A discrepancy was observed between the actual medication use and guideline recommendation while a majority of patients were undertreated.

Katherine J Baines,1,2 Juan-juan Fu,3 Vanessa M McDonald,1,2 Peter G Gibson1,2 1Faculty of Health and Medicine, Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, 2Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton, NSW, Australia; 3Respiratory Group, Department of Integrated Traditional Chinese and West Medicine, West China Hospital, Sichuan University, People’s Republic of China Background: Exacerbations of asthma and COPD are a major cause of morbidity and mortality and are responsible for significant health care costs. This study further investigates interleukin (IL)-1 pathway activation and its relationship with exacerbations of asthma and COPD. Methods: In this prospective cohort study, 95 participants with stable asthma (n=35) or COPD (n=60) were recruited and exacerbations recorded over the following 12months. Gene expressions of IL-1 pathway biomarkers, including the IL-1 receptors (IL1R1, IL1R2, and IL1RN), and signaling molecules (IRAK2, IRAK3, and PELI1), were measured in sputum using real-time quantitative polymerase chain reaction. Mediators were compared between the frequent (≥2exacerbations in the 12months) and infrequent exacerbators, and the predictive relationships investigated using receiver operating characteristic curves and area under the curve (AUC) values. Results: Of the 95 participants, 89 completed the exacerbation follow-up, where 30 participants (n=22 COPD, n=8 asthma) had two or more exacerbations. At the baseline visit, expressions of IRAK2, IRAK3, PELI1, and IL1R1 were elevated in participants with frequent exacerbations of both asthma and COPD combined and separately. In the combined population, sputum gene expression of IRAK3 (AUC=75.4%; P

Background. Common cold is one of the most frequently occurring illnesses in primary healthcare services and represents considerable disease burden. Common cold of Qi-deficiency syndrome (CCQDS) is an important but less addressed traditional Chinese medicine (TCM) pattern. We designed a protocol to explore the efficacy, safety, and optimal dose of Shen Guo Lao Nian Granule (SGLNG) for treating CCQDS. Methods/Design. This is a multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. A total of 240 eligible patients will be recruited from five centers. Patients are randomly assigned to high-dose group, middle-dose group, low-dose group, or control group in a 1 : 1 : 1 : 1 ratio. All drugs are required to be taken 3 times daily for 5 days with a 5-day follow-up period. Primary outcomes are duration of all symptoms, total score reduction on Jackson’s scale, and TCM symptoms scale. Secondary outcomes include every single TCM symptom duration and score reduction, TCM main symptoms disappearance rate, curative effects, and comparison between Jackson’s scale and TCM symptom scale. Ethics and Trial Registration. This study protocol was approved by the Ethics Committee of Clinical Trials and Biomedicine of West China Hospital of Sichuan University (number IRB-2014-12) and registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-15006349).

PURPOSE OF REVIEW A control-based asthma assessment is recommended by guidelines, but questions remain about how to assess the level of asthma control, and how current control status relates to future risks and biomarkers of disease pathogenesis. This review summarizes recent published data relating to asthma control and describes the challenges created by currently available instruments. RECENT FINDINGS The current literature continues to show the widespread use of various assessment instruments for asthma control, in particular those with composite scores. However, poor correlations exist between the different assessment tools, and these instruments lack diagnostic accuracy to differentiate uncontrolled asthma. Whereas the concept of asthma control has been extended to add an assessment of future risks to the clinical control, clinical asthma control as measured by current available assessment tools does not necessary relate to the intrinsic disease activity which is typically characterized by inflammation in asthma. SUMMARY The application of asthma control assessment represents an improvement in asthma management. The measurement of underlying disease activity potentially by biomarkers to assess disease control will lead to an improved assessment of the overall control of asthma, and further studies addressing this are needed.

IntroductionCurrent strategies for the prevention of acute exacerbations in chronic obstructive pulmonary disease (COPD) are primarily based on clinical measurements but fail to target the pathophysiological mechanisms, namely endotypes, of the disease. Studies identifying endotypes underlying exacerbation susceptibility and discovering specific biomarkers may lead to the development of targeted therapeutics but are lacking. This study aims to assess a broad spectrum of biomarkers at multiple biological levels (genetics, airway inflammation and respiratory microbiome) for their ability in predicting acute exacerbations of COPD, thus enables high-resolution disease endotyping and may lead to precision treatment of the disease.Methods and analysisIn this prospective cohort study, participants with stable COPD (n=600) will be recruited and assessed for demographics, symptom scores, spirometry, medication use and comorbidities at baseline. Blood will be obtained for genotyping variants in a panel of nine genes. Induced sputum will be collected for the profile of microbiota using 16S rRNA gene sequencing, quantification of bacterial load, inflammatory mediators assay and sputum cytometry. Participants will be followed up for their exacerbations till 12 months and reassessed for the clinical measurements as baseline. The primary outcomes are total number of exacerbations, severe exacerbations, moderate exacerbations and time to first exacerbation. The secondary outcomes are changes in lung function and symptom scores. The effect of biomarkers representing genetic variants, airway inflammation and respiratory microbiome on predicting the frequent exacerbator phenotype and exacerbation frequency will be analysed with multivariable modelling, and time to first exacerbation with a Cox regression model.Ethics and disseminationThe study has been approved by the Clinical Trial and Biomedical Ethics Committee of West China Hospital of Sichuan University (No. 2018–298). The results of the study will be published on peer-reviewed journals.Trial registration numberChiCTR1800019063.

Background: Chinese herbal medicine (CHM) has been shown to be effective in the treatment of stable chronic obstructive pulmonary disease (COPD) by published meta-analyses. However, disease outcomes were inconsistent and heterogeneity was observed attributed to placebo-controlled studies. We present a protocol for a systematic review aiming to evaluate the clinical efficacy and safety of CHM comparing to placebo in the treatment of stable COPD, to provide robust evidence for the use of CHM in COPD. Methods: We will comprehensively search the following 9 databases from inception to March 2019: Web of Science, PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese National Knowledge Infrastructure (CNKI), WANFANG Database, Chinese Scientific and Technological Periodical Database (VIP) and Chinese Biomedical Database (CBM), and the Cochrane Library database. All clinical randomized controlled trials comparing CHM to placebo for the treatment of stable COPD in English or Chinese will be included. The primary outcome will be quality of life, symptom score and exacerbation frequency, and the secondary outcomes include traditional Chinese medicine syndrome score and effective rate, lung function, 6-minute walk distance, and adverse events. Data extraction and quality assessment will be performed independently by 2 reviewers. Data synthesis and risk of bias will be assessed using the Review Manager software. This protocol will be conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidance. Results: This systematic review and meta-analysis will provide a high-quality comprehensive evaluation of the efficacy and safety based on current literature evidence of CHM intervention for stable COPD. Conclusion: The conclusion of this study will present the evidence of whether CHM is an effective and safe intervention for stable COPD patients.

Background: Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with high morbidity and mortality placing heavy social and economic burden. As a kind of complementary therapy for the treatment of stable COPD, Chinese oral herbal paste has been widely used and studied. The study aims to evaluate the clinical efficacy and safety of herbal paste in the treatment of stable COPD, and to provide evidence for its clinical application. Methods: We will electronically search databases, including Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, EMBASE, PubMed, Chinese National Knowledge Infrastructure (CNKI), WANFANG Database, Chinese Scientific and Technological Periodical Database (VIP), and Chinese Biomedical Database (CBM), from respective inception to June 2019 to collect randomized controlled trials (RCTs) of Chinese oral herbal paste for the treatment of stable COPD. The websites of Chinese clinical trial registry and international clinical trial registry, the reference lists of the retrieved articles, conference proceedings, and gray literature will also be collected. The quality of life, symptom scores, and exacerbation frequency will be measured as primary outcomes. Secondary outcomes include scores of traditional Chinese medicine (TCM) syndrome, clinical effective rates according to criteria in TCM, changes in lung function, 6-minute walking distance, and safety analysis. The Cochrane bias risk assessment and the GRADE method will be used to assess the quality of the original studies included. Merging analysis of data will be performed using Rev Man 5.3 software. Results: The systematic review will provide an evidence on the clinical efficacy and safety of Chinese oral herbal paste for the treatment of stable COPD, and will be submitted for publication in a peer-reviewed journal. Conclusion: The study will confirm whether Chinese oral herbal paste is an effective and safe intervention for the prevention and treatment of stable COPD.

Background Amino acid variations in several HCV genomic regions have been reported to be associated with response to interferon (IFN)-α plus ribavirin (RBV) combination therapy. However, the results remain controversial. In this study, we further investigated the amino acid variation of full-length HCV genome and its correlation to the response to pegylated interferon (PEG-IFN)-α2a and RBV combination therapy in patients with HCV genotype 1b (HCV-1b). Methods We retrospectively analysed 18 chronic HCV-1b patients (9 with rapid virological response and 9 non-response to therapy) treated with PEG-IFN-α2a plus RBV for 48 weeks. The nearly full-length HCV genome sequence was amplified by reverse transcription (RT)-PCR followed by cloning and sequencing. Genetic diversity differences between two groups were analysed including the number of amino acid variations in the HCV polyprotein and the mean pair-wise protein distance. Results No single amino acid variations were closely associated with treatment outcome. However, the number of amino acid mutations in the NS5B region especially in the thumb domain and in the NS5A-V3 region was associated with the response to PEG-IFN-α/RBV therapy ( P=0.002 and P=0.029, respectively). The number of substitutions in the NS5B region was significantly correlated with the numbers of substitutions in the V3 region ( r=0.568, P=0.027). Conclusions Amino acid substitutions in the NS5B region especially in the thumb domain and the NS5A-V3 region may play a role in the response to combined PEG-IFN-α2a and RBV therapy in HCV-1b patients.

Background: The progression of obstructive airway diseases (OADs) including asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome in older adults is not well understood. Objective: To examine the prognosis of OADs and to identify potential determinants for longitudinal changes in clinical outcomes. Methods: We consecutively recruited 99 older adults (>55 years) with OADs who underwent a multidimensional assessment at baseline and 4 years which involved spirometry, 6-min walk distance (6MWD), assessments of health status (Saint George's Respiratory Questionnaire, SGRQ), comorbidity, and serum and sputum biomarkers. All-cause mortality and respiratory hospitalisation during the follow-up period were recorded. Clinical outcomes were compared between basal and final visits, and changes in clinical outcomes were compared among asthma, COPD and asthma-COPD overlap groups. Associations between clinical parameters, biomarkers and prognosis were examined. Results: After a median follow-up of 4.2 years, outcome data were available for 75 (75.8%) patients. There were 16 (16.2%) deaths. The BODE index predicted all-cause mortality in older people with OADs. While spirometry, 6MWD and SGRQ deteriorated significantly over the 4 years, there was significant heterogeneity in the longitudinal changes in these clinical outcomes. Participants with COPD had a significant decline in FEV1 (p = 0.003), SGRQ (p = 0.030) and 6MWD [decline of 75.5 (93.4) m, p = 0.024]. The change in 6MWD was lower in the asthma-COPD overlap group. Airflow reversibility was associated with a reduced decline in 6MWD. Conclusion: COPD patients had a poor prognosis compared with asthma and asthma-COPD overlap patients. The BODE index is a useful prognostic indicator in older adults with OADs. Both airway disease diagnosis and BODE index warrant specific attention in clinical practice.

Systemic inflammation is reported to be associated with neutrophilic airway inflammation in asthma, but mechanisms underlying this finding are not well understood. This study aimed to examine the molecular mechanisms of the airway neutrophilia that are associated with systemic inflammation in asthma. Fifty stable nonsmoking adults with asthma had plasma high sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) assayed. Subjects with an elevation of both hsCRP and IL-6 were grouped as asthmatics with systemic inflammation, and those with both hsCRP and IL-6 within the normal ranges were grouped as asthmatics without systemic inflammation. Clinical characteristics and sputum inflammatory cell counts were compared between the two groups. Gene expression profiles from sputum were analyzed and altered expression of four genes (CCL8, IL8RA, SELL, and PI3) was confirmed using quantitative PCR. Asthmatics with systemic inflammation (n=18, 36%) had a higher BMI, greater history of cigarette smoking, lower FVC% predicted, and increased sputum neutrophils compared to those without systemic inflammation (n=16, 32%). Microarray analysis identified 449 genes that were significantly altered in sputum between the two groups. Altered genes were involved in IL-1, TNF-α/nuclear factor-κB, and Kit receptor pathways, and were related to innate immune response, defense and inflammatory response, in particular neutrophilic inflammation. Systemic inflammation was associated with airway neutrophilia in asthma, and was related to a group of differentially expressed genes in the lung involving multiple cytokine pathways. Our findings suggest that targeting systemic inflammation might provide a novel therapeutic strategy for neutrophilic asthma.

Introduction An increasing number of trials of multi-herb formula interventions are being published in relatively high-ranked medical journals indexed in the Science Citation Index Expanded (SCIE). The aim of the study was to evaluate the quality of reporting of two-group parallel randomized controlled clinical trials (indexed in SCIE) of multi-herb formulae. Methods Computerized literature searches were performed in SCIE from 1996 to November 2010. Two reviewers independently assessed the included trials using the modified Consolidated Standard of Reporting Trials (CONSORT) 2010 checklist and additional items reflecting the basic characteristics of traditional Chinese medicine (TCM). The number and proportion of reports describing each of the 38 modified CONSORT items and 6 additional TCM items were calculated. We also performed stratified analyses according to whether reports had or had not adopted the CONSORT statement, or according to Chinese reports (conducted in Mainland China, Hong Kong and Taiwan) or non-Chinese reports. Results The reporting of the items recommended by the CONSORT 2010 statement was suboptimal as only 5 items were described in more than 80% of the 153 included reports. For the recommended CONSORT items, adherence was higher in CONSORT-adopters, and more items were reported in non-Chinese reports. The reporting of the TCM items was considered inadequate in the included studies, particularly in non-Chinese reports. Conclusions The present study shows that the quality of reporting of these trials is suboptimal. We recommend all journals endorse the CONSORT statement, which would help researchers to improve the reporting of future randomized controlled trials. In addition, the reporting of the TCM items was considered inadequate in the included studies. All TCM practitioners should pay attention to the unique characteristics of TCM and improve the reporting of the recommended TCM items.

Background and objective: Postextubation problems such as laryngeal edema and reintubation are common complications after tracheal intubation. The cuff-leak test has been proposed as a method of identifying those patients at high risk in clinical practice, but its efficacy remains controversial. Methods: We searched electronic databases including PubMed, the Cochrane Controlled Trials Register, Web of Science, Ovid, and Embase. Studies were included if they were concerned with accuracy of the cuff-leak test and the effect of cuff-leak test screening on patient-important outcomes. Two reviewers independently assessed study quality with the QUADAS tool and extracted data. We compiled diagnostic two by two tables and pooled estimates of sensitivity and specificity, but refrained from pooling when there was considerable clinical or statistical heterogeneity. Results: Sixteen diagnostic tests with 3172 participants and six clinical trials with 2500 patients were identified. The median diagnostic odds ratios for predicting postextubation laryngeal edema and reintubation were 18.16 (range, 3.54 to 356.00) and 10.80 (2.74 to 1665.00), respectively. The accuracy of the cuff-leak test varied with different methods, duration of intubation, and study population. An indirect comparison found significant differences in post-extubation incidence of laryngeal edema (OR = 2.09, 95% CI, 1.28 to 2.89) but not reintubation (OR = 0.94, 95% CI, 0.32 to 1.57) if using cuff-leak test screening. Conclusions: Our results suggest the cuff-leak test accurately predicts which adult patients are at high risk of postextubation airway complications, but randomized controlled trials are needed to further assess this diagnostic strategy.

The aim of this study was to evaluate the relationship between interleukin-21 (IL-21) and interleukin-21 receptor (IL-21R) polymorphisms and the response to peginterferon alfa (PEG-IFN α) therapy in HBeAg-positive chronic hepatitis B (CHB) patients.A total of 143 HBeAg-positive CHB patients treated for 48 weeks with PEG-IFN α and followed up for 24 weeks post-treatment were retrospectively evaluated. Genotypes analysis was performed for IL-21 polymorphisms rs907715, rs2221903, and IL-21R polymorphisms rs3093301 and rs2285452. Serum IL-21 levels were measured by enzyme-linked immunosorbent assay.The end of virological response (EVR) rate was 46.9% (67/143) at the end of treatment, the sustained virological response (SVR) rate was 43.4% (62/143) and the complete response (CR) rate was 32.1% (46/143) at 24 weeks post-treatment. Patients who carried IL-21 rs 2221903 genotype AA had a rather higher rate of EVR (response rate: 52.4%, odds ratio [OR] 0.42, 95% confidence interval [CI]: 0.19-0.91, P = .021), SVR (response rate: 47.6%, OR 0.43, 95% CI: 0.19-0.95, P = .028), and CR (response rate: 38.1%, OR 0.31, 95% CI: 0.12-0.79, P = .014) when compared to those had AG genotype. Meanwhile, IL-21rs 2221903 genotype AA was also independently associated with markedly reduced HBsAg levels (>1og10 IU/mL) after 24 weeks treatment and low HBsAg levels (

Background: An increasing number of randomized placebo-controlled trials involving traditional Chinese medicine (TCM) compound formulations have been implemented worldwide. Objective: The aim of this study was to assess the reporting quality, scientific rigor, and ethics of randomized placebo-controlled trials of TCM compound formulations and compare these differences between Chinese and non-Chinese trials. Methods: English-language databases included the following: PubMed, OVID, EMBASE, and Science Citation Index Expanded. Chinese-language databases included the following: Chinese Biomedical Literature Database, Wanfang Database, Chinese Scientific and Technological Periodical Database, and the China National Knowledge Infrastructure. All were searched from respective inception to March 2009 to identify randomized placebo-controlled trials involving TCM compound prescriptions. Two reviewers independently assessed the retrieved trials via a modified Consolidated Standard of Reporting Trials (CONSORT) checklist and some evaluation indices that embodied the TCM characteristics or the scientific rigor and ethics of placebo-controlled trials. Trial publishing time was divided into 3 intervals: phase 1 (≤1999); phase 2 (2000–2004); and phase 3 (2005–2009). The number and percentage of trials reporting each item and the corresponding differences between Chinese (mainland China, Hong Kong, and Taiwan) and non-Chinese (eg, Japan, United States, Australia, Korea, and United Kingdom) trials were calculated. Moreover, the influence of trial publishing time on the reporting of CONSORT items and the differences in the number of items reported for each time interval between Chinese and non-Chinese trials were assessed. Results: A total of 324 trials from China and 51 trials from other countries were included. A mean of 39.7% of the CONSORT items across all Chinese trials and 50.2% of the items across all non-Chinese trials were reported. The number of the reported CONSORT items all increased over time in both groups and the gap between Chinese articles and non-Chinese articles gradually decreased. Additionally, of the 324 Chinese articles, 137 (42.28%) reported TCM syndrome type, 113 (34.88%) reported the diagnostic criteria of diseases for TCM, and 69 (21.30%) reported efficacy evaluation indices of TCM. Of the non-Chinese articles, 3 (5.88%) reported TCM syndrome type and 1 (1.96%) reported the diagnostic criteria of diseases and evaluation indices of efficacy for TCM. It was found that 45.37% and 6.17% of Chinese articles reported the standard intervention for the diseases being treated and the emergency plan, respectively, compared with 23.53% and 9.80% for the non-Chinese articles; 33.02% and 10.49% of Chinese articles reported informed consent and ethics committee approval, respectively, compared with 92.16% and 82.35% for the non-Chinese articles. With regard to placebo ethics, 38.89% of the Chinese trials and 23.53% of the non-Chinese trials found it would not be ethically acceptable to use placebo alone in the control group. Conclusions: The data indicate that the reporting quality of the included trials on TCM compounds has improved over time, but still remains poor regardless of Chinese or non-Chinese trials. Across all trials, particularly Chinese trials, the reporting of the CONSORT items was inadequate (39.7%). The difference in the mean number of the reported CONSORT items between Chinese trials and non-Chinese trials narrowed from phase 1 (10.0 vs 13.8) to phase 3 (14.4 vs 17.4). Moreover, a large number of trials, especially non-Chinese trials (94.1%), were lacking syndrome differentiation of TCM. More importantly, in many placebo-controlled trials, especially Chinese trials, the use of placebo was not justified and was ethically contradictory.

Airway hyperresponsiveness (AHR) is the characteristic functional abnormality of asthma, and previous studies have shown the potential for AHR to be influenced by psychological factors, yet the relationship between anxiety and/or depression and AHR remains unclear in patients with asthma.To explore the relationship between psychological status and AHR in asthma patients.In a cross-sectional study, 168 adult subjects were recruited with physician-diagnosed uncontrolled asthma and a positive result for AHR in methacholine (Mch) challenge test. Psychological status, asthma control, and asthma quality of life were assessed using Zung self-rating anxiety/depression scale, asthma control test (ACT), and asthma quality of life questionnaire (AQLQ), respectively. AHR severity was evaluated and quantified by the provocative concentration of Mch, which evoked a given decrease of 20% in FEV(1).A total of 70.23% of recruited patients (n = 118) met the diagnostic criteria for anxiety and/or depression. There was a trend between negative psychological status and AHR in asthma patients that did not reach statistical significance, but no independent effects of negative mood states (anxiety, depression, or both) on AHR were established. Further, analyses revealed that only anxiety is associated with worse asthma control (p = 0.029), and a significant interaction effect of depression and anxiety accounted for lower asthma-related quality-of-life scores (p0.001).AHR and psychological status are loosely related to each other even if in uncontrolled asthma.

Objective To evaluate the efficacy and safety of new drugs of traditional Chinese medicine (TCM) for acute upper respiratory tract infection (common cold). Methods Reports regarding randomized controlled trials of Chinese medicine for common cold were reviewed. Related reports were selected and the methodological quality of the trials was assessed by the Jadad scale. Meanwhile, the stratified analysis was made according to different TCM syndrome types of common cold. Results Thirteen randomized controlled trials consistent with the inclusion criteria were selected and reviewed. As TCM treatment group was compared with control group, the meta analysis indicated that the relative risk (RR) for obviously effective rate was 1.10, and the 95% confidence interval (CI) was [1.05, 1.16]; the weighted mean difference (WMD) of the onset time of lowering body temperature was -1.70, and the 95% CI was [-2.76, -0.65]. There were significant differences in the above evaluation indexes between the two groups (P=0.000 2, P=0.002). The WMD of disappearing time of fever was -1.32, and the 95% CI was [-3.14, 0.49], while there was no significant difference between the two groups (P=0.15). As the common cold patients with wind-heat syndrome in the TCM treatment group were compared with those in the control group, the meta analysis indicated that the RR for obviously effective rate was 1.11, the 95% CI was [1.05, 1.19], and there was significant difference between the two groups (P=0.000 7). As the common cold patients with wind-cold syndrome in the TCM treatment group were compared with those in the control group, the meta analysis indicated that the RR for obviously effective rate was 1.07, the 95% CI was [0.99, 1.16], and there was no significant difference between the two groups (P=0.10). Serious adverse reactions had not been reported in the trials. Conclusion TCM new drugs developed in recent years for preventing and treating common cold have better therapeutic effects than the old ones. They can accelerate the onset time of lowering body temperature and improve the symptoms of common cold without any significant adverse reactions. Because of lacking of placebo-controlled and blank-controlled studies, further high-quality trials are still needed.

Multi-exponential inversion of NMR (Nuclear Magnetic Resonance) relaxation signal has been widely used in petroleum industry both in core analysis for petrophysical studies and in logging interpretation for oil exploration. In order to obtain T2 relaxation time distributions with high resolution in the case of low SNR (Signal-to-Noise Ratio), we use simulated and experimental data to analyze the effects on the inversion of the number of pre-selected relaxation times, the number of spin echoes acquired, and the compression in time domain of the spin-echo trains. We found that reducing the number of echoes acquired can cause divergent behavior for the long T2 components, changing the number of windows for data compression does not change the shape of the inverted T2 distribution significantly. We also studied the effect of different SNRs on inverted T2 distributions for different inversion algorithms. We found that the response to different SNRs for different algorithms is different, and suggested using an adjustment parameter to correct such effects.

Background: Asthma-COPD overlap syndrome (ACOS) is commonly present in patients with chronic airway disease. This study aimed to describe the characteristics and medication use of the patients admitted with acute exacerbation of ACOS. Methods: We retrospectively analyzed patients with doctor diagnosed ACOS that had acute exacerbations admitted from January 2011 to December 2014 in a tertiary hospital. Patients with pneumonia and respiratory disorders other than asthma and COPD were excluded. Clinical characteristics, comorbidity, arterial blood gas, complete blood count, blood chemistry tests, routine sputum culture, chest radiography and medication use were assessed. Features of the patients that used systemic glucocorticoids were further analyzed. Results: A total of 146 patients were evaluated.The median length of hospital stay was 12(9-15) days. Chest radiology was available in 138(94.5%) patients of which 81.9% had the sign of chronic bronchitis or emphysema. The average PO 2 and PCO 2 in arterial blood gas were 76.5(65.2-96.1) mmHg and 43.0(38.4-49.1) mmHg. Twelve (8.2%) patients were on NIV and 4(2.7%) received intubation. While positive bacterial pathogen on sputum culture was found in 52(35.6%) patients, 132(90.4%) patients used antibiotics. Hospital length of stay was greater in patients that used systemic glucocorticoid (61.6%, 13(10-16)) than those did not (38.4%, 11(7.5-14)) (P=0.016), while the majority of characteristics at admission were not different between the two groups. Conclusion: Characteristics of the exacerbations of ACOS with different severities and that compared to asthma and COPD as well as appropriate medication use need to be further investigated.

Background: A significant proportion of patients with chronic airways disease present asthma and COPD overlap syndrome (ACOS). Acute exacerbation of ACOS required hospitalisation is also assumed to be a major cause of morbidity and accounts for significant medical cost, in which hospital length of stay (LOS) is a significant marker of clinical severity and use of medical resources. This study aimed to determine the factors associated with hospital LOS in acute exacerbations of ACOS. Methods: A retrospective cohort study was conducted to assess patients with doctor diagnosed ACOS that had acute exacerbations admitted from January 2011 to December 2014. Patients with pneumonia and respiratory disorders other than asthma and COPD were excluded. Clinical characteristics, comorbidity, arterial blood gas, complete blood count, blood chemistry tests,routine sputum culture, chest radiography and medication use were assessed. Stepwise negative binomial regression was performed to identify factors associated with hospital LOS in exacerbations of ACOS. Results: A total of 146 patients were evaluated with the median LOS of 12(9-15) days. Multivariate negative binomial regression analysis identified that age starting to present respiratory symptoms ( P =0.001), Charlson index of comorbidity( P =0.002), positive bacterial pathogen on sputum culture ( P =0.002) and the use systemic glucocorticoid ( P =0.009) were independently associated with increased hospital LOS in acute exacerbations of ACOS. Conclusion: Several factors were associated with hospital LOS in patients with acute exacerbations of ACOS which may be useful for prediction of clinical outcomes of ACOS.